Although rates of cigarette smoking are declining in the general population, rates of smoking among people with schizophrenia remain markedly high. Quit rates in these smokers are virtually zero. Few studies have systematically examined biological and behavioral factors that affect smoking in this population. The long-term objectives of this research program are to learn how biological and behavioral variables contribute to smoking addiction in these patients, and to use this information to develop strategies of reducing smoking in people with schizophrenia. This study will investigate, under laboratory conditions, the separate and combined effects of nicotine replacement (42 mg versus placebo) and sensorimotor replacement (access to denicotinized cigarettes versus no access) on smoking behavior in smokers with schizophrenia. We will also investigate effects in smokers who are matched on age, gender distribution, daily smoking rate and nicotine dependence, but do not have current psychiatric illness. We will also investigate effects of these interventions on urges to smoke, nicotine withdrawal symptoms, psychiatric symptoms, and cognitive task performance, and examine whether effects on these variables mediate effects on smoking. Relevance: We anticipate that this project will expand existing knowledge concerning factors that affect smoking in people with schizophrenia and heavy smokers without current mental illness. In turn, this information could be used to develop novel treatment strategies for these smokers.